Greentree Group Publishers
Received 03/04/20 Accepted 10/05/2020 Published 10/05/2020
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Int J Ayu Pharm Chem REVIEW ARTICLE www.ijapc.com
e-ISSN 2350-0204
ABSTRACT
Glaucoma is a neurodegenerative disease of the optic nerve and the second leading causes of
vision loss in the world among the geriatric population. Apoptosis is a programmed cell death
causing damage to Retinal ganglion cells (RGCs) resulting in death of the cell. Alzheimer’s
disease (AD) is a neurodegenerative disease characterized by dementia in geriatric population.
Glaucoma and Alzheimer’s disease are having similarities in neuropathology and are
progressive neurodegerative diseases. The loss of large magnocellular RGCs in optic nerve are
seen in Glaucoma and Alzheimer Disease. The elevated glutamate level and nitric oxide
synthase up regulation with reactive oxygen species formation are the excitotoxic triggers
noted in both disease.
Brain is the seat of Indriyas, Manas, Prana. Pradnya or Budhi is the ultimate function of these
three factors of brain. The anatomical or physiological disturbances in the brain will ultimately
affect the Pradnya. Levels of management are
i. Primary: Natural protective provision,
ii. Secondary: Protective measures for healthy personnel,
iii. Tertiary: Protection at neurological level.
On these three levels Ayurveda can tackle the neurodegeneration and can prevents the neural
loss in diseases like Glaucoma. The recent advances can also be considered in treatment of
Glaucoma on following levels: Neuroprotection, Neuroenhancement, Retinal Ganglion Cell
Replacement, optic nerve regeneration & vision restoration. The present paper will give a new
insights and addition in the knowledge of scientific Ayurvedic community.
KEYWORDS
Glaucoma, Alzheimer, Apoptosis, Neuroprotection, Ayurveda
Ocular Alzheimer’s-Disease and Ayurveda- An Integrated
Approach and New Insight for Research
Pravin M Bhat1*, Hari N Umale2
1Dept. of Shalakyatantra, Sumatibhai Shah Ayurved College, Hadapsar, Pune (M.S), India
2Dept. of Shalakyatantra, Govt. Ayurved College & Hospital, Nagpur (M.S), India
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INTRODUCTION
Adhimantha is a Sarvagat Vyadhi and can
be symptomatically equally compared to
Glaucoma which is the second cause of
blindness and can cause irreversible
damage in eyes leading to irreversible loss
of vision1. The causative factors of
development of retinal/optic nerve damage
and loss of visual function are still
unknown. The raised intraocular pressure
(IOP), auto regulation of retinal blood
supply, apoptosis of retinal ganglion cells
(RGCs) in the individual patient,
connective tissue at the lamina cribrosa, and
perfusion pressure are the risk factors for
the disease glaucoma. Medicinal line of
treatment is only aimed towards the
regulation of Intra Ocular Pressure but over
the period of time apoptosis starts causing
the damage to nerve fibers and retinal
ganglion cell leading to visual field loss2.
The number of glaucoma cases are
increasing worldwide from 60 million to 80
million cases by 2020 with the prevalence
rate 2.65% in people above the age of 40
years. The prevalence rate of Primary open
angle glaucoma (POAG) is more than that
of Primary angle closure glaucoma
(PCAG). Glaucoma is the subsequent major
reason of blindness after cataract and
refractive errors and falls under the
category of irreversible blindness. It is
estimated that in excess of 3 million
individuals are visually handicapped
because of glaucoma3.
EPIDEMIOLOGY
In India, 12 million cases are affected with
glaucoma which is the one fifth of the
global cases of glaucoma. According to
Vellore Eye Study (VES), Prevalence of
POAG, PACG, and ocular hypertension
were 4.1, 43.2 and 30.8 per 1,000,
respectively, that is, 0.41%, 4.32% and
3.08%, respectively. According to Andhra
Pradesh Eye Disease Study (APEDS)
definite POAG, suspected POAG, and OHT
had an age- and gender adjusted prevalence
of 1.62%, 0.79%, and 0.32% in those 30
years of age or more, and 2.56%, 1.11%,
and 0.42% in those 40 years of age or more,
respectively. According to Arvind
Comprehensive Eye Survey, the prevalence
of any glaucoma was 2.6%, of POAG it was
1.7%, and if PACG it was 0.5%, and
secondary glaucoma excluding
pseudoexfoliation was 0.3% 4.
So the average prevalence rate of POAG to
be considered for the study is 1.24%. Most
of the time the cases of glaucoma were
undiagnosed and identified during the
survey (98.6% in the Chennai Glaucoma
Study and 93% in ACES). According to the
National Blindness survey 2001, glaucoma
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is the third major cause of blindness in India
and cause 5.9% of blindness (VA <6/60)5.
The proportion of blindness caused due to
glaucoma has increased three times
compared to that found in the previous
National survey in between the years 1986–
19896. It is seen that glaucoma visual
impairment is disparaged in these surveys
as the blindness is characterized on visual
acuity criteria rather than visual fields
which is main feature of glaucoma.
Glaucoma is a chronic, neurodegenerative
disease that originates with pressure-
induced changes at the optic nerve head
(ONH) and subsequent death of retinal
ganglion cells (RGCs) with an associated
loss of vision. Glaucoma research, similar
to that of other neurodegenerative diseases,
has seen an increasing focus on
neuroprotection7. There is no specific
targeted therapy for neuroprotection in
glaucoma.
APOPTOSIS AND GLAUCOMA
Around half of the ganglion cells do not
make central connection within the lateral
geniculate nucleus in primates and die from
apoptosis. Apoptosis was also involved in
the IOP elevation process, by altering the
structure of trabecular meshwork and
disrupting aqueous humor outflow.
Apoptosis is a programmed cell death
initiated because of glutamate toxicity and
oxidative stress in the cell which causes
death of adjacent cell causing progressive
visual field defect.
ALZHEIMER DISEASE
Alzheimer’s disease (AD) is termed as a
progressive neurodegenerative condition in
which the progressive developement of
dementia in older age occurs.
Neuropathological findings in AD consist
of neurofibrillary tangles and deposition of
amyloid in neuritic plaques concentrated in
the hippocampal and parahippocampal
areas of brain8. Amyloid deposition occurs
through the abnormal proteolytic
processing of the integral membrane
protein amyloid precursor protein (APP),
yielding an abnormal accumulation of
amyloid-beta peptide consisting of 40 or 42
amino acids9. Alzheimer's disease is an age-
related, chronic, progressive
neurodegenerative disease and is
characterized by severe loss of memory,
unusual behavior, changes in personality,
and a decreased in cognitive function.
SIMILARITIES BETWEEN
GLAUCOMA AND ALZHEIMER
DISEASE
There are multiple similarities noted in
neuropathology of Glaucoma and
Alzheimer’s disease which are chronic
neurodegenerative conditions. Loss of large
magnocellular RGCs seen in optic nerve in
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patients of Alzheimer’s disease. These type
of cells dies earliest in glaucoma10. The
triplet neurofilament proteins that are
components of pathological neurofibrillary
tangles also demonstrate localization to
large RGCs11,12. The elevated glutamate13,
14 and nitric oxide synthase up regulation
with reactive oxygen species formation15
have been seen in glaucoma which are
excitotoxic triggers. The same process can
be observed in Alzheimer’s disease16. The
increased susceptibility to excitotoxic
injuries caused due to synaptic dysfunction
in AD which is associated with deficient
glutamate transport function17,18 and
caspase activity19.
The perimetry of mildly affected AD
patients shown the visual field defects
reported by some studies20. The visual field
defects in AD patients significantly seen in
the infero-temporal and infero-nasal
arcuate regions, in a pattern that is very
much mimicking to visual field loss in
glaucoma. As compare to the open angle
glaucoma patients, the visual field loss has
been more prominent and occurs at a
greater rate in AD patients21.
VASCULAR PATHOLOGY IN
GLAUCOMA AND ALZHEIMER
DISEASE
The cerebral amyloid angiopathy (CAA)
are caused by vascular deposits of amyloid-
beta in AD. The CAA causes degeneration
of vascular endothelial and smooth muscle
cells22,23 and hemorrhagic stroke24.
Amyloid-beta1-40 is found in vasculature
of AD patients, whereas amyloid-beta1-42
is reported in senile plaques25.
Some of the studies reported that vascular
amyloid deposition may occur in glaucoma.
The pathology of glaucoma is expected to
occur because of the high levels of amyloid-
beta1-40 and other APP fragments that
cause a type of cerebral amyloid angiopathy
(CAA) that affects the blood vessels of the
retina and optic nerve head26. This provides
a clue for pathology of splinter
haemorrhages in glaucoma patients. Some
study findings showed delayed course of
apoptosis in AD patients because of caspase
activation27, 28.
AIMS & OBJECTIVES
Acharya Charaka stated in Siddhisthana
about the importance of Trimarma (Shiro,
Hriday, Basti) as “The vital breath of
human resides in heart, head and urinary
bladder. Therefore one needs to make every
effort to protect them. Protecting vital parts
means preventing imminent causes,
adhering to code of conduct for the healthy
and remedying the condition if it occurs29”.
So considering the principle of protection
of the seat of Prana i.e. Murdhni (brain) the
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neuroprotective levels can be planned for
treatment.
MECHANISM OF
BUDDHIBHRANSHA
The Buddhi (Prajnya) is the ultimate
function of the factors Indryas, Manas and
Prana residing within the brain. When any
disruption occurs either at structural or
functional level in the brain, the Prajnya is
directly affected.
LEVELS OF NEUROPROTECTION
Since the neuroprotective strategies are
gaining the uprising wave in the field of
ophthalmology research, the current
integration between AD and Glaucoma will
help to discover the newer treatment
modalities in Ayurveda. As per Acharya
Charaka the Marmapalana (protection of
Trimarma) Siddhant can be categorized on
following three levels
i. Primary: Natural Protective
provisions.
ii. Secondary: Protective measures for
healthy personnel.
iii. Tertiary: Protection at neurological
level.
Primary level of neuroprotection includes
bony protection, soft tissue protection, CSF
protection, healthy compartments of brain,
auto regulation. As per Ayurveda Murdha
(brain) is the seat of Prana, Indriya and
Mana. The physiological aspect of the
organ is essential in primary level of
neuroprotection.
Secondary level of protection includes
Ayurvedic strategies like Garbhini
Paricharya, Prasuti Paricharya, Shishu
Paricharya, Swasthavritta Paricharya, use
of Panchakarma treatment, Rasayan,
Dharaniya and Adharniya Vega,
Trayopastambha Paripalan and Yoga and
Pranayam.
According to modern science control of
B.P, control of lipids, control of sugar,
avoidance of narcotics, alcohol, smoking,
stress, fast food, use of organic food, etc.
Tertiary protection includes the
Panchakarma therapies like Shirodhara,
Shirobasti to alleviate vitiated Vata Dosha.
Medhya Rasayana is useful to nourish the
brain tissue and Sarvadehik Rasa Dhatu.
Satvik diet, Satvovajay Chikitsha i.e patient
and family counselling. One can use
Suvarna Bhasma, Roupya Bhasma or a
combination of it.
NEWER AREA OF RESEARCH
IN GLAUCOMA30
Glaucoma is a chronic condition in which
there is gradual loss of vision due to damage
to the optic nerve. In present era, no
treatment modality can reverse the loss of
vision due to glaucoma. New ways to treat,
control and even cure glaucoma are
important for patients and doctors. The key
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areas of research in glaucoma identified as
are
NEUROPROTECTION
It is a capacity to keep the retinal ganglion
cells (RGCs) alive and strengthen their
health regardless of the damage occurred by
glaucoma. Neuroprotection can be studied
with animal studies.
NEUROENHANCEMENT
It is the modality that one can give the cells
a “booster shot” and make the sick cells
functional again to gain vision in short time
duration.
REPLACEMENT OF RGCS
Replacement is done with two key
approaches:·
Endogenous RGC Replacement requires
the use of existing cell sources including
Müller glia, retinal pigment epithelial cells,
and stem cells. The efficient
reprogramming of these cells is required to
make functional RGCs.
Exogenous RGC replacement includes
using outside sources to generate RGCs,
such as induced pluripotent stem cells.
REGENERATION OF OPTIC NERVE
Stimulates the development of axons
through an optic nerve injury site to suitable
target areas of the brain while preventing
abnormal development.
RESTORATION OF VISION
The restoration of vision includes restoring
vision that was already lost due to
glaucoma. It depends on the ability of brain
to recognize to retain some functions.
DISCUSSION
The present review suggest a hypothesis for
RGC death in glaucoma involving chronic
amyloid-beta neurotoxicity which is similar
to that of Alzheimer’s disease for the
treatment objective in Ayurveda. The
potential benefits from this review are that
ayurvedic treatments contemplated for
Alzheimer’s disease may be used to treat
glaucoma. Conversely, the neuroprotective
approaches designed for the treatment of
glaucoma may also be used for other
chronic neurodegenerative conditions as
per Ayurveda. The single herbs like
Ashwangadha (Withania somnifera),
Haridra (Curcuma longa), Kapikachhu
(Mucuna pruriens), Bramhi (Bacopa
monniera), Punarnava (Boerhavia diffusa),
Triphala (trio of T. chebula, T. bellerica
and E. officinalis) are some of the
indigenous medicines which can be tested
for the neuroprotective effect and their
Chakshyushya properties. The animal
models can be designed to study the
neuroprotection in Glaucoma and the
Ayurvedic drugs mentioned in Alzheimer’s
disease (particularly Medhya Rasayan) can
be tested in animal models of glaucoma.
The glaucoma that can be easily studied on
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an animal model having key features as
axonal injury at the nerve head as an initial
feature of damage, and, selective RGC loss
with sparing of other retinal neurons. The
pathophysiology of glaucoma is complex
and difficult to study in humans. As such,
one can rely on animal models that
faithfully reproduce important aspects of
the condition for understanding
mechanisms of disease and developing new
therapies. Animal glaucoma models are
important for our ongoing efforts to
elucidate the disease's natural course and
establish therapeutic approaches to delay or
reverse the condition's progression. So the
animals are necessary in the regards of
neuroprotection study of Glaucoma. The
present review emphasizes on the study of
glaucoma pathway in regards with the
pathophysiology of AD through Ayurvedic
treatment modalities in animals.
ACKNOWLEDGEMENT
Article by Stuart J Mckinnon on Glaucoma:
Ocular Alzheimer’s disease published in
Frontiers in Bioscience, October 2003.
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